tbuckley/cabot-search huggingface dataset:
Effect of socioeconomic status as measured by Neighborhood Deprivation Index on survival in metastatic breast cancer.
Authors: Susrutha Puthanmadhom Narayanan, Margaret Q. Rosenzweig, Dianxu Ren, Steffi Oesterreich, Adrian V. Lee, Adam Brufsky
Journal: Journal of Clinical Oncology (2022)

1013 Background: Socioeconomic status (SES) and race are major determinants of health outcomes in the United States. We aim to assess the effect of SES as measured by the Neighborhood Deprivation Index (NDI) and race on outcomes in metastatic breast cancer patients at our center. Methods: The NDI scores for patients with metastatic breast cancer who were treated at our center between 2000 and 2017 were obtained from the Neighborhood Atlas using their Zip-Code (N = 1246). The SES groups were defined as low deprivation with an NDI score in the bottom tertile and high deprivation with NDI in the top or middle tertiles. Baseline characteristics were compared between the SES groups with Bonferroni correction. Univariate and multivariate survival analysis were performed using the R packages “survival” and “survminer”. Results: Race was the only baseline characteristic that was significantly different between the SES groups, the high deprivation group had a higher proportion of African Americans (10.5%) than the low deprivation group (3.7%, P = 9.3e-05). In univariate Kaplan-Meier survival analysis, both SES and race had significant effect on overall survival such that the high deprivation group had worse survival than low deprivation (Log Rank P = 0.01) and African Americans had worse survival than Caucasians (P = 0.008). In multivariate Cox proportional hazard model, SES, but not race, had a significant effect on overall survival (hazard ratio for high deprivation was 1.19 [95% Confidence interval 1.04 - 1.37], P = 0.01; Table). Progression-free survival on first-line chemotherapy was not different between the SES groups or racial groups in both univariate and multivariate analysis. Conclusions: The current study shows that patients from the high deprivation group (i.e., low SES), have worse survival in metastatic breast cancer. Race was no longer a significant predictor of survival when SES was accounted for in the analysis. This possibly suggests that poor outcomes in the African American population is explained by the association between low SES and African American race. Based on these results, there is an urgent need for healthcare investments in the low SES neighborhoods. [Table: see text]
Delaying post-operative radiation therapy after radical prostatectomy is associated with increased functional outcomes: Results from a large single, referral center series
Authors: M. De Angelis, E. Mazzone, G. Gandaglia, A. Stabile, S. Scuderi, F. Barletta, D. Robesti, L. Nocera, R. Leni, V. Cucchiara, A. Necchi, E. Zaffuto, N. Suardi, S. Shariat, F. Montorsi, A. Briganti
Journal: European Urology (2022)
Clinical and biological features prognostic of survival after relapse of INRGSS-stage MS pattern neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project.
Authors: Kevin M. Campbell, Pei-Chi Kao, Arlene Naranjo, Takehiko Kamijo, Ramya Ramanujachar, Wendy B. London, Steven G. DuBois
Journal: Journal of Clinical Oncology (2022)

10044 Background: Neuroblastoma (NB) presenting with INRGSS MS metastatic pattern highlights the extreme heterogeneity within NB and subsequent difficulty in risk assignment. Depending on tumor biology, patients with stage MS disease may be classified as very-low risk or as high-risk. While outcomes at initial diagnosis have been well-described, outcomes after relapse are less well defined. Methods: From the INRG Data Commons, we investigated clinical and biological characteristics of patients diagnosed 1984-2021 with stage MS pattern NB (INSS stage 4s, INSS stage 4 or INRG stage MS) who subsequently experienced disease relapse or progression, excluding patients whose first event was death. Using Kaplan-Meier methods, post-relapse overall survival (OS)± standard error (SE) was calculated from the time of first relapse/progression until death or last contact, overall and by era of diagnosis: &lt; 2000 vs ≥2001. Univariate Cox models were used to identify factors prognostic of post-relapse OS. Results: 209 patients met eligibility criteria,103 diagnosed &lt; 2001 and 106 ≥2001. Of patients diagnosed ≥2001, 89% (n = 94) were &lt; 365 days old at diagnosis; tumors were MYCN amplified in 21% (21/102) and diploid in 31% (20/64). Of this same cohort, time from initial diagnosis to relapse was &lt; 6 months in 40% (n = 42), 6-12 months in 25% (n = 26), and &gt; 12 months in 36% (n = 38) of patients. Of 60 patients with known site of relapse/progression diagnosed ≥2001, 73% (44) were metastatic (29) or primary plus metastatic (15). Among these, 16% (5/32) remained stage MS pattern while 84% (27/32) had metastatic sites beyond MS sites. Five-year post-relapse OS±SE was 53±3.5% overall (n = 209), and higher for those diagnosed ≥2001 (62±5.0%; n = 106) compared to those diagnosed &lt; 2001 (44±4.9%; n = 103) (p = 0.0046). In patients diagnosed ≥2001, factors prognostic of superior post-relapse OS included: age &lt; 365 days; not Hispanic; MYCN non-amplified; no 1p loss/aberration, hyperdiploidy; low/intermediate MKI; LDH &lt; 1400 U/L, favorable INPC histology; and &lt; 12 months from initial diagnosis to first relapse. Conclusions: Most patients with relapsed stage MS NB have metastatic relapse and these relapses more commonly occur at sites outside liver, skin, and bone marrow. Patients diagnosed ≥2001 with MS pattern NB have substantially better post-relapse OS compared to those diagnosed &lt; 2001. In the cohort of patients with MS pattern NB diagnosed ≥2001, most of the well-accepted prognostic factors for OS at diagnosis are also prognostic of post-relapse OS.
CD4+ T helper 2 cells suppress breast cancer by inducing terminal differentiation
Authors: Margherita Boieri, Anna Malishkevich, Ranya Guennoun, Emanuela Marchese, Sanne Kroon, Kathryn E. Trerice, Mary Awad, Jong Ho Park, Sowmya Iyer, Johannes Kreuzer, Wilhelm Haas, Miguel N. Rivera, Shadmehr Demehri
Journal: The Journal of Experimental Medicine (2022)

Cancer immunology research is largely focused on the role of cytotoxic immune responses against advanced cancers. Herein, we demonstrate that CD4+ T helper (Th2) cells directly block spontaneous breast carcinogenesis by inducing the terminal differentiation of the cancer cells. Th2 cell immunity, stimulated by thymic stromal lymphopoietin, caused the epigenetic reprogramming of the tumor cells, activating mammary gland differentiation and suppressing epithelial–mesenchymal transition. Th2 polarization was required for this tumor antigen–specific immunity, which persisted in the absence of CD8+ T and B cells. Th2 cells directly blocked breast carcinogenesis by secreting IL-3, IL-5, and GM-CSF, which signaled to their common receptor expressed on breast tumor cells. Importantly, Th2 cell immunity permanently reverted high-grade breast tumors into low-grade, fibrocystic-like structures. Our findings reveal a critical role for CD4+ Th2 cells in immunity against breast cancer, which is mediated by terminal differentiation as a distinct effector mechanism for cancer immunoprevention and therapy.
LGG-10. Evaluation of the chemotherapy efficacy of children with optic pathway glioma in a tertiary hospital in China
Authors: Miao Li, Shuxu Du, Yongji Tian, Jin Zhang, Wenchao Gao, Jinjing Xiao, Xiaojun Gong, Yanling Sun, Wanshui Wu, Liming Sun
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE: In order to analyze the chemotherapy efficacy of children with optic pathway glioma (OPG), the clinical, treatment and prognosis factors of children with OPG who received the German International Society of Pediatric Oncology (SIOP) low-grade glioma (LGG) 2004 regimen chemotherapy, were retrospectively analyzed. METHOD: From September 2014 to October 2019, a total of 60 patients with OPG were enrolled and accept LGG 2004 chemotherapy in the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, China. The progression-free survival (PFS) rates and overall survival (OS) rates were analyzed by the Kaplan-Meier method. Both univariate and multivariate analyses were performed using the Cox-proportional hazards model. The test standard α=0.05. RESULTS: Until January 1st, 2022, all children were alive, and the clinical symptoms were improved at any degree, and well tolerated during the whole treatment. The median follow-up time was 3.7 years (range 2.3-7.1 years), the average time of objective response was 6.8 months (range from 2 to 21 months), and the 5 year PFS rates were 73.0 ± 7.24 %. However, about 3 to 8 months later, 8 cases (age &amp;lt;4 years) relapsed which attained partial remission (PR) at the end of the whole therapy. These relapsed cases were performed the LGG 2004 regimen again, and all had an objective response after 4~6 courses of treatment. In addition, two children (age&amp;gt;8 years old) progressed rapidly during treatment, and had to be performed local radiotherapy and reached complete remission (CR). Another two cases with BRAF V600E mutation, reached a significant remission after 3 months of targeted therapy with selumetinib. Furthermore, the COX multivariate analysis shows that spinal metastasis is an independent risk factor of prognosis of children with OPG. CONLUSIONS: Chemotherapy can improve the clinical efficacy of children with OPG, which is better when combining with bevacizumab and/or targeted therapy.
Sintilimab versus pembrolizumab in monotherapy or combination with chemotherapy as first-line therapy for advanced non–small cell lung cancer: Results from phase 2, randomized clinical trial (CTONG1901).
Authors: Si-Yang Maggie Liu, Qing Zhou, Hong-Hong Yan, Gan Bin, Ming-Yi Yang, Jia-Yi Deng, Hai-Yan Tu, Xuchao Zhang, Jian Su, Jinji Yang, Yi-Long Wu
Journal: Journal of Clinical Oncology (2022)

9032 Background: Immunotherapy has become standard therapy for untreated advanced NSCLC. However, no direct comparison between anti-PD-1 inhibitors has been reported. Methods: CTONG1901 is an open label, randomized, phase II clinical trial to compare sintilimab and pembrolizumab in monotherapy or combination with chemotherapy for advanced NSCLC at first-line setting. The primary endpoint was objective response rate (ORR). Patient without EGFR and ALK alteration were enrolled. Patients with PD-L1 tumor proportion score (TPS) ≥50% were randomly to receive sintilimab (A) or pembrolizumab (B) ; and with TPS&lt;50% were randomly to receive sintilimab (C) or pembrolizumab (D) combined with chemotherapy. Sample size was calculated by Optimal Two-Stage Designs. 20 patients were enrolled in 1 st stage. When ≥4 patients achieve partial response (PR) in sintilimab arms, the study will enter into 2 nd stage and the sample size will be calculated based on the ORR results of the 1 st stage. Results: The ORR was 57.1% in sintilimab and 33.3% in pembrolizumab arms at the 1 st stage. The study successfully entered into the 2 nd stage. 48 additional patients should be enrolled after calculation. When 15 PR in sintilimab arms achieved, the primary endpoint will be reached. From Mar. 2020 to Jan. 2022, 71 patients were screened and 68 patients were enrolled in two stages. Histologic subtypes and brain metastasis were well balanced between arms. As of Dec. 31 st 2021, the median follow-up was 5.6 months. The confirmed ORR was 45.5% (15/33) in sintilimab vs. 28.6% (10/35) in pembrolizumab arms (A vs. B: 30.8% [4/13] vs. 28.6% [4/14]; C vs. D: 55.0% [11/20] vs. 28.6% [6/21]). Unconfirmed ORR was 57.6% vs. 42.9% and disease control rate (DCR) was 87.9% vs. 91.4% in sintilimab and pembrolizumab arms. The primary endpoint was reached. Survival data was immature. Any grade and 3-4 grade treatment-related adverse events (TRAEs) were comparable in sintilimab and pembrolizumab arms (Table). Conclusions: This is the first head-to-head phase II study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced NSCLC. The result suggested comparable tumor response and similar safety profile between sintilimab and pembrolizumab. Clinical trial information: NCT04252365. [Table: see text]
Prognostic Implications of N-Terminal Pro–B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin T in EMPEROR-Preserved
Authors: James L. Januzzi, Javed Butler, Faiez Zannad, Gerasimos Filippatos, João Pedro Ferreira, Stuart J. Pocock, Naveed Sattar, Subodh Verma, Ola Vedin, Tomoko Iwata, Martina Brueckmann, Milton Packer, Stefan D. Anker
Journal: JACC Heart Failure (2022)

N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are associated with disease severity and outcomes among patients with heart failure (HF) with preserved ejection fraction.The authors evaluated associations between both biomarkers and clinical outcomes in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) trial.Of 5,988 study participants, 5,986 (99.9%) and 5,825 (97.3%) had available baseline NT-proBNP and hs-cTnT; postbaseline NT-proBNP was also available. Baseline characteristics were expressed by biomarker quartiles. The effect of empagliflozin on cardiovascular death/ HF hospitalization, the individual components, total HF hospitalizations, slope of decline of estimated glomerular filtration rate (eGFR), and a composite renal endpoint were examined across biomarker quartiles. Change in NT-proBNP across study visits as a function of treatment assignment was also assessed.Higher baseline NT-proBNP and hs-cTnT concentrations were associated with more comorbidities and worse HF severity. Incidence rates for cardiac and renal outcomes were 2- to 5-fold higher among those in the highest vs lowest NT-proBNP or hs-cTnT quartiles. Empagliflozin consistently reduced the risk for cardiovascular events and reduced slope of eGFR decline across NT-proBNP or hs-cTnT quartiles. Empagliflozin treatment modestly lowered NT-proBNP; by 100 weeks, the adjusted mean difference in NT-proBNP from placebo was 7%. Increase in NT-proBNP from baseline to 12 weeks was strongly associated with risk of cardiovascular death/HF hospitalization.The benefit of empagliflozin on cardiac outcomes and decline of eGFR is preserved across the wide range of baseline NT-proBNP and hs-cTnT evaluated. Empagliflozin modestly reduces NT-proBNP in HF with preserved ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT03057951).
Population-wide patterns of care in chronic lymphocytic leukemia in Australia: An analysis of the pharmaceutical benefits scheme dataset.
Authors: Shu Chuen Li, Fei-Li Zhao, Raj Gauba, Keri Yang, Soraya Azmi, Constantine Si Lun Tam
Journal: Journal of Clinical Oncology (2022)

e19518 Background: The treatment landscape in patients with chronic lymphocytic leukemia (CLL) is changing with the approvals of Bruton’s tyrosine kinase inhibitors (BTKis) in Australia. We sought to understand the practice impact of the introduction of publicly funded novel agents for the treatment of CLL. The objective of this study was to describe the evolving treatment patterns of Australian patients with CLL over the last 10 years using population-wide prescription records. Methods: Patients who initiated a treatment for CLL between 01/01/2011 and 07/31/2021 were extracted from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset. This dataset includes the dispensing records for 10% of the Australian population and captures all publicly funded treatments in Australia. The index date was defined as the commencement of any drug for the treatment of CLL. First-line (1L) therapy was defined as the first treatments prescribed for CLL. A patient was defined as relapsed/refractory (R/R) if they had commenced a drug which was in a different therapeutic category, or if they re-started the same regimen after a gap of more than 180 days. Descriptive analyses were conducted to examine the use of treatment regimens for the overall 10-year population by line of therapy. Analyses by calendar year were also performed to assess changes in treatment patterns. Results: Overall, 803 patients with CLL were identified. The majority of patients were male (65%) and age &gt; 60 years (77%), with most being aged 70-79 years (33% of total). Many patients were receiving comedications at baseline, including antihypertensives (47%), antipsychotics or antidepressants (17%), and/or anticoagulants (13%). In the overall population (2011-2021), the majority of patients had received 1L treatment with fludarabine-cyclophosphamide-rituximab (FCR, 49%), chlorambucil ± CD20 (27%), or CD20 monotherapy (17%). The most commonly used regimens in R/R patients at any subsequent episode of treatment included CD20 monotherapy (56%), BTKi (41%) or FCR (33%). A trend in adoption of novel agents was observed throughout the years following their PBS listing. Analysis by calendar year showed that from 2011 to 2020 use of FCR in 1L decreased from 78% to 10%; and use of BTKis in R/R increased from 0% to 62%. Conclusions: CLL treatment patterns have significantly changed in Australia since the introduction of the BTKis (e.g., ibrutinib, acalabrutinib). The use of FCR in 1L CLL has decreased and use of BTKis in R/R patients has increased.
EPEN-15. Radiotherapy with helium ions has the potential to improve both endocrine and neurocognitive outcome in pediatric patients with ependymoma
Authors: Ricarda Wickert, Sebastian Adeberg, Maximilian Deng, Thomas Tessonnier, Line Hoeltgen, Jürgen Debus, Klaus Herfarth, Semi Harrabi
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Ependymoma are the third most frequent pediatric brain tumors. To prevent local recurrence, the resection site should be irradiated. Especially the treatment of pediatric patients requires precise dose application and optimal protection of organs at risk. Compared to photon radiation treatment, proton therapy often achieves better results regarding target coverage and organ-sparing. Due to their physical properties, helium ions can further reduce side effects, providing better protection of healthy tissue despite similar target coverage. PATIENTS AND METHODS: In our in-silico study, 15 pediatric patients (median age six years) with ependymoma located in the posterior cranial fossa were considered. All patients underwent adjuvant radiotherapeutic treatment with active scanned protons at Heidelberg Ion-Beam Therapy Center (HIT). Both helium ion and highly conformal IMRT plans were calculated to evaluate the potential dosimetric (and clinical) benefit of ion beam therapy compared to the current state of the art photon-based treatments. RESULTS: Target coverage was comparable in all three modalities (He, H+, Ph): homogeneity indices (HI) and inhomogeneity coefficients (IC) of HIHe=5.8±3.8, HIH+=7.5±4.0, HIPh=6.4±4.3, ICHe=0.2±0.1, ICH+=0.2±0.1, ICPh=0.2±0.1. As expected, the integral dose absorbed by the healthy brain tissue could be reduced significantly using helium ions versus IMRT (-45.3%±15.1%). Based on our preliminary results, even compared to active scanned protons – currently the most precise radiation technique worldwide – the relative dose reduction for critical neuronal structures using helium ions on average amounts to -27.2%±14.4%. CONCLUSION: Previous studies could clearly demonstrate that the dosimetric advantage of protons translates into a measurable clinical benefit for pediatric patients with brain tumors. Given the dose response relationship of critical organs at risk, the results of our in-silico study provide a strong rationale that the use of helium ions has the potential to even further reduce the risk for treatment related sequelae.
Management of Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases: ASCO Guideline Update
Authors: Naren Ramakrishna, Carey K. Anders, Nancy U. Lin, Aki Morikawa, Sarah Temin, Sarat Chandarlapaty, Jennie R. Crews, Nancy E. Davidson, Maria Alice B. Franzoi, Jeffrey J. Kirshner, Ian E. Krop, Debra A. Patt, Jane Perlmutter, Sharon H. Giordano
Journal: Journal of Clinical Oncology (2022)

PURPOSE To provide updated evidence- and consensus-based guideline recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer up to 2021. METHODS An Expert Panel conducted a targeted systematic literature review (for both systemic therapy for non-CNS metastases and for CNS metastases of HER2+ guideline updates) that identified 545 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events. RESULTS Of the 545 publications identified and reviewed, six on systemic therapy were identified to form the evidentiary basis for the systemic therapy for CNS metastases guideline recommendations. RECOMMENDATIONS Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Memantine and hippocampal avoidance should be added to whole-brain radiotherapy when possible. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. There are insufficient data to recommend for or against performing routine magnetic resonance imaging to screen for brain metastases; clinicians should have a low threshold for magnetic resonance imaging of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer. Additional information is available at www.asco.org/breast-cancer-guidelines .